Abstract
Oxidized phospholipids (OxPLs) on apolipoprotein B-100 (apoB-100) particles are strongly associated with lipoprotein [a] (Lp[a]). In this study, we evaluated whether Lp[a] is preferentially the carrier of OxPL in human plasma. The content of OxPL on apoB-100 particles was measured with monoclonal antibody E06, which recognizes the phosphocholine (PC) headgroup of oxidized but not native phospholipids. To assess whether OxPLs were preferentially bound by Lp[a] as opposed to other lipoproteins, immunoprecipitation and ultracentrifugation experiments, in vitro transfer studies, and chemiluminescent ELISAs were performed. Immunoprecipitation of Lp[a] from human plasma with an apolipoprotein [a] (apo[a])-specific antibody demonstrated that more than 85% of E06 reactivity (i.e., OxPL) coimmunoprecipitated with Lp[a]. Ultracentrifugation experiments showed that nearly all OxPLs were found in fractions containing apo[a], as opposed to other apolipoproteins. In vitro transfer studies showed that oxidized LDL preferentially donates OxPLs to Lp[a], as opposed to LDL, in a time- and temperature-dependent manner, even in aqueous buffer. Approximately 50% of E06 immunoreactivity could be extracted from isolated Lp[a] following exposure of plasma to various lipid solvents. These data demonstrate that Lp[a] is the preferential carrier of PC-containing OxPL in human plasma. This unique property of Lp[a] suggests novel insights into its physiological function and mechanisms of atherogenicity.
Highlights
Oxidized phospholipids (OxPLs) on apolipoprotein B-100 particles are strongly associated with lipoprotein [a] (Lp[a])
In study 1, plasma was repeatedly obtained from 1 subject with elevated Lp[a] levels, but without cardiovascular disease (CVD), for immunoprecipitation and ultracentrifugation experiments; in study 2, plasma was obtained from 14 subjects without CVD for detailed ultracentrifugation experiments; and in study 3, plasma was obtained from 12 subjects with familial hypercholesterolemia undergoing apheresis, 9 of whom had a history of CVD
This study documents that PC-containing OxPLs recognized by E06 are nearly exclusively bound to Lp[a], as opposed to other lipoproteins, in human plasma
Summary
Oxidized phospholipids (OxPLs) on apolipoprotein B-100 (apoB-100) particles are strongly associated with lipoprotein [a] (Lp[a]). We evaluated whether Lp[a] is preferentially the carrier of OxPL in human plasma. Immunoprecipitation of Lp[a] from human plasma with an apolipoprotein [a] (apo[a])-specific antibody demonstrated that more than 85% of E06 reactivity (i.e., OxPL) coimmunoprecipitated with Lp[a]. 50% of E06 immunoreactivity could be extracted from isolated Lp[a] following exposure of plasma to various lipid solvents These data demonstrate that Lp[a] is the preferential carrier of PC-containing OxPL in human plasma. This unique property of Lp[a] suggests novel insights into its physiological function and mechanisms of atherogenicity.—Bergmark, C., A. A novel function of lipoprotein [a] as a preferential carrier of oxidized phospholipids in human plasma. There is little evidence to support such a role in vivo
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